Antiinflammatory properties of the new antirheumatic agent 4-acetylaminophenylacetic acid

The antiinflammatory activity of 4-acetylaminophenylacetic acid (MS-932) was investigated. MS-932 did not suppress the acute inflammation of carrageenin-induced paw edema in rats or of primary swelling in adjuvant arthritic rats. However, prophylactic treatment with MS-932 inhibited secondary inflammation in adjuvant arthritic rats. MS-932 also restored to normal the weight of the spleen and the serum albumin/globulin ratio of adjuvant arthritic rats. In addition to its prophylactic effect, MS-932 had a therapeutic effect on adjuvant arthritis. In in vitro tests, MS-932 did not inhibit prostaglandin E2 biosynthesis from arachidonic acid by sheep seminal vesicle microsomal enzyme or superoxide generation by guinea pig neutrophils stimulated with opsonized zymosan. MS-932 had no analgesic effect in mice and no antipyretic effect in rats. These results indicate that MS-932 suppresses adjuvant arthritis through modulation of the immune system.     

Analysis of the determinant factors for open heart surgery without blood transfusion by the quantification theory--possibility of application of maximum surgical blood order schedule for open heart surgery]

In order to complete operations without blood transfusion we have chosen means of preoperative autologous blood saving and intraoperative autotransfusion, but we have not always achieved our purpose. We examined 29 patients (13 patients without blood transfusion and 16 with blood transfusion) to analyze the determinant factors as to whether open heart surgery without blood transfusion may be indicated or not, according to the quantification theory (type II) and to examine the possibility to apply the maximum surgical blood order schedule (MSBOS) for the open heart surgery by the quantification theory (type I). The analysis of determinant factors revealed hematocrit (Ht) value before saving of blood (more than 40%) as the best contributor of possibility of non-blood transfusion surgery, followed by the amount of blood loss during operation (less than 600 ml), the amount of saving blood (more than 800 ml), body weight (less than 70 kg), calculated Ht value on the beginning of cardiopulmonary bypass (CPB) (more than 24%), CPB time (less than 120 minutes) and the amount of postoperative blood loss (less than 600 ml). The prospective using blood volume at the operation was precisely calculated by the values of 4 preoperative factors, that is, the amount of saving blood, calculated Ht value on the beginning of CPB, CPB time and body weight. Therefore it is important to increase the amount of preoperative saving blood and decrease the amount of surgical bleeding in order to perform operations without blood transfusion, and is possible to apply the MSBOS for the open heart surgery.     

A new myeloblastic leukemia cell line with double minute chromosomes. Induction of methotrexate resistance and dihydrofolate reductase gene amplification.

To test the relationship between DMs and drug resistance in newly established AML cell lines, KY821, and its clone KY821A3, the latter had lost DMs during cloning, were cultured in increasing concentrations of MTX. KY821 became resistant against 2 x 10(-4) M MTX, whereas KY821A3 did against 2 x 10(-5) M MTX in a same period. Enhanced enzyme activities of DHFR were correspondent to the increased DMs numbers and DHFR gene amplification in both resistant clones. The amplified DHFR gene was located on DMs by in situ hybridization. These data indicated that the presence of DMs in KY821 would facilitate the acquisition of drug resistance.     

Hematopoietic recovery in a patient with acute lymphoblastic leukemia after an autologous marrow graft purged by combined hyperthermia and interferon in vitro.

We describe a patient with acute lymphoblastic leukemia (ALL) in whom hemopoiesis recovered after an autologous marrow graft purged by in vitro hyperthermia. A 17-year-old woman was diagnosed as having ALL in April 1985. After clinical remission was induced, marrow cells were harvested. The marrow cells were treated with hyperthermia at 42.0 degrees C for 1 h in the presence of alpha-interferon to eliminate residual leukemic cells, and then cryopreserved. In January 1990, during her fourth remission she was treated with busulfan and cyclophosphamide, and then received the thawed autologous marrow. Her hematopoietic recovery was prompt with normal trilineage regeneration without any life-threatening complications. She is in good health without evidence of a leukemic relapse at 6 months after autologous bone marrow transplantation. This case suggests that human multilineage progenitor cells retain self-renewal capacity in vivo even after treatment with heat and alpha-interferon in vitro followed by the freezing and thawing procedures.     

Visual evoked potentials relating to imagery: Words for concrete objects versus absolute concepts

Summary We recorded visual evoked potentials (VEPs) elicited with high or low imaginable Chinese characters (HIC or LIC), representing concrete objects or absolute concepts, respectively. A closed circle (CC) acts as control stimulus. These were displayed (at 1.6° visual angle) for 35 ms on a TV monitor. Twenty-one channel VEPs (band-pas filter: 0.05–60 Hz), using balanced non-cephalic electrodes, were recorded from –100 to 924 ms for 11 right-handed male volunteers. The VEPs were analyzed by multivariate analysis of variance (MANOVA) and comparison of topographies at four remarkable peaks (P110, N160, P230 and N320). MANOVA showed significant differences (p< 0.001) for both conditions of channel and stimuli (HIC, LIC or CC). P100 for the CC-VEPs, N160 for the HIC-and LIC-VEPs, P230 for the CC-VEPs, and N320 for the HIC-VEPs were remarkable in the posterior scalp regions. Topographies at P100 and N160 showed no difference between the HIC-and LIC-stimuli. However, those at N320 showed difference between the HIC-and LIC-stimuli over the occipital and posterior temporal areas. Those results suggest that the responses at P100 and N160 might segregate Chinese characters from non Chinese characters. N320 suggested certain processes in imagery on recognizing Chinese characters over the occipital and posterior temporal areas.We are grateful to Dr. Yoshiji Kojima of Hamamatsu University for helpful comments.     

The relation between EEG and mental development following cardiac surgery performed under simple deep hypothermia in children

In order to assess the accuracy of electroencephalography (EEG), in children who have undergone cardiac surgery under simple deep hypothermia, the relation between IQ or schoolwork achievement and the duration of circulatory arrest was investigated in 75 such children. Abnormal preoperative EEG's were found in 16 per cent of the children while abnormal postoperative EEG's were found in 17 per cent. The children were divided into 4 groups, according to pre- and postoperative EEG results. Schoolwork achievement scores ranged between 3.0 and 3.2, the difference among the groups being insignificant. Moreover, no significant shift in IQ was found among the groups. Finally, regarding the number of children who were able to go on to a higher level of education, including high school the college or university, again no significant differences were found among the 4 groups. In a comparison with the number of such children in neighboring Nagasaki prefecture able to continue on to a higher level of education, no significant differences were seen either. The findings and statistics of this investigation therefore indicate that pre- and postoperative EEG's are not always a reliable reference for assessing the prognosis of cerebral activity.     

Effects of KT-362, a new calcium release blocker, on vascular selectivity and hemodynamic actions in anesthetized dogs

Pharmacological properties of 5-(3-((2-(3,4-dimethoxyphenyl)ethyl)-amino)-1- oxopropyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine fumarate (KT-362), a newly synthesized calcium release blocker, were studied by comparing its vascular selectivity and cardiovascular actions with those of verapamil, a calcium entry blocker. The relaxing effect of KT-362 in rabbit femoral and basilar artery strips contracted with norepinephrine was greater than that in aortic and coronary artery strips. In anesthetized mongrel dogs, KT-362 (0.1-3.0 mg/kg, i.v.) decreased the mean blood pressure, heart rate and total peripheral resistance in a dose-dependent manner, while cardiac output increased slightly despite a decrease in left ventricular pressure. This is consistent with the data on verapamil. Both i.a. and i.v. injections of KT-362 produced a marked dose-dependent increase in vertebral and femoral blood flow. Pretreatment of atropine, propranolol or diphenhydramine exerted no significant effect on the KT-362-induced vasodilation. Verapamil caused a marked increase in the vertebral and coronary blood flows after the injections, but only a slight increase in femoral blood flow. KT-362 at the dose of 10 mg/kg, i.v., had no significant effect on the PQ interval on the electrocardiogram in anesthetized dogs, but 0.1 mg/kg of verapamil increased this interval significantly. These results suggest that KT-362 has properties similar to calcium entry blockers such as verapamil on systemic hemodynamic actions except for the reactivity of vasculatures.     

Effect of radiation therapy on extracerebral cavernous hemangioma in the middle fossa. Report of three cases

Intracerebral cavernous hemangiomas are relatively easy to remove surgically, but extracerebral cavernous hemangiomas attached to the cavernous sinus are extremely difficult to treat. The authors report three cases of extracerebral cavernous hemangioma in the middle fossa that were treated with radiotherapy. The follow-up studies with serial computerized tomography (CT) scans during and after irradiation are described. In Case 1 radiotherapy after partial removal of the tumor decreased the tumor size on the contrast-enhanced CT scans, reduced its Hounsfield units on the nonenhanced CT scans, and facilitated later total tumor removal. In Case 2 the tumor responded to irradiation with approximately 3000 rads, showing significant reduction in size and Hounsfield units of the tumor. Subtotal removal was then possible. In Case 3 the tumor responded to irradiation, and the patient's vertigo improved after delivery of approximately 3000 rads. The CT scan showed significant reduction in the size and Hounsfield units of the tumor. No surgical intervention was deemed necessary. It is concluded that, in cases of extracerebral cavernous hemangioma with massive hemorrhage, irradiation with up to 3000 rads may be the treatment of choice. Radiation therapy offers an increased probability of total removal of the tumor and the possibility of eliminating surgery.     

Phase II study of etoposide (VP-16) in the form of intravenous injection for malignant lymphomas and acute leukemias: Hanshin Cooperative Study Group for Hematological Disorders

Twenty patients with malignant lymphomas and 12 with acute leukemias were treated with intravenous administration of etoposide, 60-100 mg/m2/day for five days, repeated for three to four weeks. Eighteen cases of malignant lymphoma and nine of acute leukemia were evaluable. CR was achieved in three cases (16.7%) and PR in four cases (22.2%) of malignant lymphoma. Although CR was not achieved in any patients with acute leukemia, and PR was in three (33.3%), it was found that etoposide was most effective for the patients with the M4 or M5 subtype in the FAB classification. The most serious adverse effect of the drug was leukopenia in patients with lymphoma. In three patients (30.0%), the leukocyte count was lower than 1,000/mm3. Gastrointestinal complications, such as anorexia, nausea, vomiting and diarrhea occurred in 60.7% of all patients, but were not serious. Alopecia was observed in 73.1%. Intravenous administration of etoposide was apparently effective for the patients with malignant lymphoma of the diffuse mixed type, and this efficacy found in our study was the same as that for oral administration of etoposide reported by us previously.